文献类型：期刊文献

中文题名：pH/温度刺激响应型核-壳结构介孔二氧化硅纳米颗粒的设计与制备

英文题名：Design and Preparation of pH/Temperature Stimulated Responsive Core-Shell Mesoporous Silica Nanoparticles

作者：陈昊文[1];陈淼鑫[1];刘晔宏[1];张钰华[1];徐首红[1]

机构：[1]华东理工大学化学与分子工程学院,结构可控先进功能材料及其制备教育部重点实验室,上海200237

年份：2022

卷号：35

期号：2

起止页码：155

中文期刊名：功能高分子学报

外文期刊名：Journal of Functional Polymers

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(21776071,22078087)。

语种：中文

中文关键词：原子转移自由基聚合;多重刺激响应;介孔二氧化硅纳米颗粒;药物控释

外文关键词：atom transfer radical polymerization;multiple stimulus response;mesoporous silica nanoparticle;controlled drug release

摘要：首先将具有pH敏感特性的聚甲基丙烯酸二异丙胺基乙酯(PDPA)和靶向分子叶酸(FA)接枝到介孔二氧化硅纳米颗粒(MSNs)表面,合成了MSNs-PDPA-FA。然后将单体甲基-2-丙烯酸-2-(2-甲氧基乙氧基)乙酯(MEO_(2)MA)、聚乙二醇甲醚甲基丙烯酸酯(OEGMA)与甲基丙烯酸二异丙胺基乙酯(DPA)通过原子转移自由基聚合(ATRP)反应制备了pH/温度双重响应型聚合物P(MEO_(2)MA_(90)-co-OEGMA_(10))-b-PDPA10。最后在pH=7.4的条件下将聚合物P(MEO_(2)MA_(90)-co-OEGMA_(10))-b-PDPA_(10)通过疏水作用自组装到MSNs-PDPA-FA的壳层来保护FA分子。通过粒径与透射率表征分析了该自组装体的pH/温度响应性能,并对该自组装纳米载体的体外释药动力学进行了研究。结果表明,该自组装体系能够灵敏地响应环境中pH与温度的变化。在正常生理环境下,48 h后的药物累计释放量不超过10%,而在pH=5.0、44℃下,药物48 h的累计释放量达到65%。
Premature leakage of drugs into the bloodstream remains a problem in the process of drug delivery,resulting in higher toxic and side effects on normal tissue cells.Novel drug carriers enabling effective drug accumulation in the tumor site have got much attention of researchers.Poly(methyl acrylic acid diisopropyl amino ethyl ester)(PDPA)is a polymer with pH-sensitive response,the diisopropylamine in the side chains are protonated in an acidic environment,resulting in its changing from hydrophobic to hydrophilic.PDPA was grafted onto the surface of mesoporous silica nanoparticles(MSNs)by atom transfer radical polymerization(ATRP)reaction.Then folic acid(FA)was introduced onto PDPA as a targeting ligand for enabling the drug carrier to enter tumor cells effectively.Simultaneously poly[di(ethylene glycol)methyl ether methacrylate-co-oligo(ethylene glycol)methacrylate]-b-poly[methyl acrylic acid diisopropyl amino ethyl ester](P(MEO_(2)MA_(90)-co-OEGMA_(10))-b-PDPA_(10))with dual sensitivity of temperature and pH was synthesized and the lower critical solution temperatures(LCST)of the polymer was adjusted to 44℃by adjusting the proportion of three monomers.A drug carrier with a core-shell structure was self-assembled through hydrophobic force by covering the later polymer on the surface of MSNs-PDPA-FA.Finally,the drug release kinetics of the carrier was studied by using doxorubicin(DOX)as a model drug,and the result showed that the total leakage of the model drug DOX was less than 10%after 48 h in normal physiological environment(pH=7.4,37℃).However,when the pH value was changed to 5.0 at 44℃,the shell was dissociated from the core and the drug was released.Then,the drug was released rapidly within 5 h and the cumulative drug release could reach to 65%in 48 h.Therefore,this research was expected to construct a shielding system based on the pH/temperature dual-responsive polymer,which could be used to avoid premature exposure of certain functional groups or molecules to the normal physiological environment,and it could also prevent the premature release of drugs in the normal tissues.